4IJ9

Bovine PKA C-alpha in complex with 2-[[5-(4-pyridyl)-1H-1,2,4-triazol-3-yl]sulfanyl]-1-(2-thiophenyl)ethanone

Summary for 4IJ9

• Entry DOI: 10.2210/pdb4ij9/pdb
• Related: 4ie9
• Descriptor: cAMP-dependent protein kinase catalytic subunit alpha, cAMP-dependent protein kinase inhibitor alpha, 2-[[5-(4-pyridyl)-1H-1,2,4-triazol-3-yl]sulfanyl]-1-(2-thiophenyl)ethanone, ... (4 entities in total)
• Functional Keywords: protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Bos taurus (bovine); More
• Cellular location: Cytoplasm : P00517
• Total number of polymer chains: 2
• Total formula weight: 43235.20

Authors

Dreyer, M.K.,Schiffer, A. (deposition date: 2012-12-21, release date: 2013-05-01, Last modification date: 2017-11-15)

Primary citation

Skjaerven, L.,Codutti, L.,Angelini, A.,Grimaldi, M.,Latek, D.,Monecke, P.,Dreyer, M.K.,Carlomagno, T.
Accounting for Conformational Variability in Protein-Ligand Docking with NMR-Guided Rescoring
J.Am.Chem.Soc., 135:5819-5827, 2013

PubMed Abstract: A key component to success in structure-based drug design is reliable information on protein-ligand interactions. Recent development in NMR techniques has accelerated this process by overcoming some of the limitations of X-ray crystallography and computational protein-ligand docking. In this work we present a new scoring protocol based on NMR-derived interligand INPHARMA NOEs to guide the selection of computationally generated docking modes. We demonstrate the performance in a range of scenarios, encompassing traditionally difficult cases such as docking to homology models and ligand dependent domain rearrangements. Ambiguities associated with sparse experimental information are lifted by searching a consensus solution based on simultaneously fitting multiple ligand pairs. This study provides a previously unexplored integration between molecular modeling and experimental data, in which interligand NOEs represent the key element in the rescoring algorithm. The presented protocol should be widely applicable for protein-ligand docking also in a different context from drug design and highlights the important role of NMR-based approaches to describe intermolecular ligand-receptor interactions.

PubMed: 23565800
DOI: 10.1021/ja4007468

Experimental method

X-RAY DIFFRACTION (2.55 Å)